ABSTRACT Recent years have seen a boon in the development of new molecular, genetic and imaging tools designed to dissect brain circuits that give rise to behavior in live animals. Although investment in these efforts is yielding fantastic returns, an accounting of the definition and function of neuronal circuits underlying higher mental function requires that these tools be extending into animal models capable of performing more sophisticated cognitive tasks. Ideally, this would be an animal model with a brain that most closely resembles that of the human brain. One such model is the rhesus macaque monkey. New world monkeys such as the marmoset are gaining increasing attention due to the possibility of developing a transgenic primate, but it is the old world, rhesus monkey in which we have the benefit of 40+ years of anatomical and physiological data from sensory and motor systems, and moreover, the behavioral sophistication of the rhesus money is unparalleled. Here we propose to extend the state of the art, live animal imaging techniques initially developed for use in the mouse, to the rhesus monkey. We will design, manufacture, optimize and test a two-channel, wireless miniaturized microscope for imaging two fluorophores to track the activity patterns of large neuronal cell populations in behaving monkeys. Features will include: 1. Larger, more sensitive, mutli-megapixel imaging sensors and objective lens arrays that will allow much larger field of view imaging (3 X 3 mm) at cellular resolution. 2. Electronic components for prolonged wireless recordings with larger batteries with a goal of 6 hour continuous recordings. 3. Electronic components that will allow synchronization of multiple microscopes used simultaneously in the same animal. 4. Features to allow drug delivery and optogenetics using the same device. We will capitalize on our existing tools developed from our mouse Miniscopes as well as the existing infrastructure developed from our current BRAIN Initiative and NSF Neuronex Hub award to add to our online environment (miniscope.org) for sharing our microscopes with the neuroscience community, lifting barriers for others to build, modify, and implant the microscopes and analyze neuronal activity data with our software. Our new wearable microscopes will have a transformative impact on neuroscience by permitting for the first time the imaging and manipulation of the activity of tens of thousands of identified neurons in behaving monkeys.